An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: 4-hydroxybenzoyl-CoA reductase
Reaction: benzoyl-CoA + oxidized ferredoxin + H2O = 4-hydroxybenzoyl-CoA + reduced ferredoxin
Other name(s): 4-hydroxybenzoyl-CoA reductase (dehydroxylating); 4-hydroxybenzoyl-CoA:(acceptor) oxidoreductase; benzoyl-CoA:acceptor oxidoreductase
Systematic name: benzoyl-CoA:oxidized ferredoxin oxidoreductase
Comments: A molybdenum-flavin-iron-sulfur protein that is involved in the anaerobic pathway of phenol metabolism in bacteria. A ferredoxin with two [4Fe-4S] clusters functions as the natural electron donor [3].
References:
1. Glockler, R., Tschech, A. and Fuchs, G. Reductive dehydroxylation of 4-hydroxybenzoyl-CoA to benzoyl-CoA in a denitrifying, phenol-degrading Pseudomonas species. FEBS Lett. 251 (1989) 237-240. [PMID: 2753161]
2. Heider, J., Boll, M., Breese, K., Breinig, S., Ebenau-Jehle, C., Feil, U., Gad'on, N., Laempe, D., Leuthner, B., Mohamed, M.E.S., Schneider, S., Burchhardt, G. and Fuchs, G. Differential induction of enzymes involved in anaerobic metabolism of aromatic compounds in the denitrifying bacterium Thauera aromatica. Arch. Microbiol. 170 (1998) 120-131. [PMID: 9683649]
3. Breese, K. and Fuchs, G. 4-Hydroxybenzoyl-CoA reductase (dehydroxylating) from the denitrifying bacterium Thauera aromatica - prosthetic groups, electron donor, and genes of a member of the molybdenum-flavin-iron-sulfur proteins. Eur. J. Biochem. 251 (1998) 916-923. [PMID: 9490068]
4. Brackmann, R. and Fuchs, G. Enzymes of anaerobic metabolism of phenolic compounds. 4-Hydroxybenzoyl-CoA reductase (dehydroxylating) from a denitrifying Pseudomonas species. Eur. J. Biochem. 213 (1993) 563-571. [PMID: 8477729]
5. Heider, J. and Fuchs, G. Anaerobic metabolism of aromatic compounds. Eur. J. Biochem. 243 (1997) 577-596. [PMID: 9057820]
Accepted name: 2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing]
Reaction: (1) a (2E)-2-enoyl-CoA + NADP+ = a (2E,4E)-2,4-dienoyl-CoA + NADPH + H+
(2) a (2E)-2-enoyl-CoA + NADP+ = a (2E,4Z)-2,4-dienoyl-CoA + NADPH + H+
Other name(s): fadH (gene name); 4-enoyl-CoA reductase (NADPH) (ambiguous); 4-enoyl coenzyme A (reduced nicotinamide adenine dinucleotide phosphate) reductase (ambiguous); 4-enoyl-CoA reductase (ambiguous); 2,4-dienoyl-CoA reductase (NADPH) (ambiguous); trans-2,3-didehydroacyl-CoA:NADP+ 4-oxidoreductase
Systematic name: (2E)-2-enoyl-CoA:NADP+ 4-oxidoreductase
Comments: This bacterial enzyme catalyses the reduction of either (2E,4E)-2,4-dienoyl-CoA or (2E,4Z)-2,4-dienoyl-CoA to (2E)-2-enoyl-CoA. The enzyme from Escherichia coli contains FAD, FMN, and an [4Fe-4S] iron sulfur cluster. cf. EC 1.3.1.124, 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 82869-38-3
References:
1. Dommes, V., Luster, W., Cvetanovic, M. and Kunau, W.-H. Purification by affinity chromatography of 2,4-dienoyl-CoA reductases from bovine liver and Escherichia coli. Eur. J. Biochem. 125 (1982) 335-341. [PMID: 6749495]
2. Dommes, V. and Kunau, W.H. 2,4-Dienoyl coenzyme A reductases from bovine liver and Escherichia coli. Comparison of properties. J. Biol. Chem. 259 (1984) 1781-1788. [PMID: 6363415]
3. You, S.Y., Cosloy, S. and Schulz, H. Evidence for the essential function of 2,4-dienoyl-coenzyme A reductase in the β-oxidation of unsaturated fatty acids in vivo. Isolation and characterization of an Escherichia coli mutant with a defective 2,4-dienoyl-coenzyme A reductase. J. Biol. Chem. 264 (1989) 16489-16495. [PMID: 2506179]
4. He, X.Y., Yang, S.Y. and Schulz, H. Cloning and expression of the fadH gene and characterization of the gene product 2,4-dienoyl coenzyme A reductase from Escherichia coli. Eur. J. Biochem. 248 (1997) 516-520. [PMID: 9346310]
5. Liang, X., Thorpe, C. and Schulz, H. 2,4-Dienoyl-CoA reductase from Escherichia coli is a novel iron-sulfur flavoprotein that functions in fatty acid β-oxidation. Arch. Biochem. Biophys. 380 (2000) 373-379. [PMID: 10933894]
6. Hubbard, P.A., Liang, X., Schulz, H. and Kim, J.J. The crystal structure and reaction mechanism of Escherichia coli 2,4-dienoyl-CoA reductase. J. Biol. Chem. 278 (2003) 37553-37560. [PMID: 12840019]
7. Tu, X., Hubbard, P.A., Kim, J.J. and Schulz, H. Two distinct proton donors at the active site of Escherichia coli 2,4-dienoyl-CoA reductase are responsible for the formation of different products. Biochemistry 47 (2008) 1167-1175. [PMID: 18171025]
Accepted name: 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing]
Reaction: (1) a (3E)-3-enoyl-CoA + NADP+ = a (2E,4E)-2,4-dienoyl-CoA + NADPH + H+
(2) a (3E)-3-enoyl-CoA + NADP+ = a (2E,4Z)-2,4-dienoyl-CoA + NADPH + H+
Other name(s): SPS19 (gene name); DECR1 (gene name); DECR2 (gene name); Δ2,Δ4-dienoyl-CoA reductase (ambiguous)
Systematic name: (3E)-3-enoyl-CoA:NADP+ 4-oxidoreductase
Comments: This enzyme, characterized from eukaryotic organisms, catalyses the reduction of either (2E,4E)-2,4-dienoyl-CoA or (2E,4Z)-2,4-dienoyl-CoA to (3E)-3-enoyl-CoA. The best substrates for the enzyme from bovine liver have a chain-length of 8 or 10 carbons. Mammals possess both mitochondrial and peroxisomal variants of this enzyme. cf. EC 1.3.1.34, 2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing].
References:
1. Kunau, W.-H. and Dommes, P. Degradation of unsaturated fatty acids. Identification of intermediates in the degradation of cis-4-decenoly-CoA by extracts of beef-liver mitochondria. Eur. J. Biochem. 91 (1978) 533-544. [PMID: 729581]
2. Dommes, V., Luster, W., Cvetanovic, M. and Kunau, W.-H. Purification by affinity chromatography of 2,4-dienoyl-CoA reductases from bovine liver and Escherichia coli. Eur. J. Biochem. 125 (1982) 335-341. [PMID: 6749495]
3. Gurvitz, A., Rottensteiner, H., Kilpelainen, S.H., Hartig, A., Hiltunen, J.K., Binder, M., Dawes, I.W. and Hamilton, B. The Saccharomyces cerevisiae peroxisomal 2,4-dienoyl-CoA reductase is encoded by the oleate-inducible gene SPS19. J. Biol. Chem. 272 (1997) 22140-22147. [PMID: 9268358]
4. Geisbrecht, B.V., Liang, X., Morrell, J.C., Schulz, H. and Gould, S.J. The mouse gene PDCR encodes a peroxisomal δ2, δ4-dienoyl-CoA reductase. J. Biol. Chem. 274 (1999) 25814-25820. [PMID: 10464321]
5. De Nys, K., Meyhi, E., Mannaerts, G.P., Fransen, M. and Van Veldhoven, P.P. Characterisation of human peroxisomal 2,4-dienoyl-CoA reductase. Biochim. Biophys. Acta 1533 (2001) 66-72. [PMID: 11514237]
6. Alphey, M.S., Yu, W., Byres, E., Li, D. and Hunter, W.N. Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase: enzyme-ligand interactions in a distinctive short-chain reductase active site. J. Biol. Chem. 280 (2005) 3068-3077. [PMID: 15531764]
[EC 1.3.7.9 Transferred entry: 4-hydroxybenzoyl-CoA reductase. Now classified as EC 1.1.7.1, 4-hydroxybenzoyl-CoA reductase. (EC 1.3.7.9 created 2000 as EC 1.3.99.20, transferred 2011 to EC 1.3.7.9, deleted 2020)]
[EC 1.6.99.3 Deleted entry: NADH dehydrogenase. The activity is covered by EC 7.1.1.2, NADH:ubiquinone reductase (H+-translocating) (EC 1.6.99.3 created 1961 as EC 1.6.2.1, transferred 1965 to EC 1.6.99.3, modified 2018, deleted 2020)]
Accepted name: thiocyanate desulfurase
Reaction: thiocyanate + 2 ferricytochrome c + H2O = cyanate + sulfur + 2 ferrocytochrome c + 2 H+
Other name(s): TcDH; thiocyanate dehydrogenase
Systematic name: thiocyanate:cytochrome c oxidoreductase (cyanate and sulfur-forming)
Comments: The enzyme, characterized from the haloalkaliphilic sulfur-oxidizing bacterium Thioalkalivibrio paradoxus, contains three copper ions in its active site. It catalyses the direct conversion of thiocyanate into cyanate and elemental sulfur without involvement of molecular oxygen.
References:
1. Tikhonova, T.V., Sorokin, D.Y., Hagen, W.R., Khrenova, M.G., Muyzer, G., Rakitina, T.V., Shabalin, I.G., Trofimov, A.A., Tsallagov, S.I. and Popov, V.O. Trinuclear copper biocatalytic center forms an active site of thiocyanate dehydrogenase. Proc. Natl. Acad. Sci. USA (2020) . [PMID: 32094184]
Accepted name: L-tyrosine peroxygenase
Reaction: L-tyrosine + H2O2 = L-dopa + H2O
Systematic name: L-tyrosine:hydrogen-peroxide oxidoreductase (L-dopa-forming)
Comments: The enzyme from the bacterium Streptomyces lincolnensis participates in the biosynthesis of the antibiotic lincomycin A, while that from Streptomyces refuineus is involved in anthramycin biosynthesis. The enzyme, which contains a heme b cofactor, is rapidly inactivated in the presence of hydrogen peroxide, but the presence of L-tyrosine protects it. cf. EC 1.11.2.5, 3-methyl-L-tyrosine peroxygenase.
References:
1. Neusser, D., Schmidt, H., Spizek, J., Novotna, J., Peschke, U., Kaschabeck, S., Tichy, P. and Piepersberg, W. The genes lmbB1 and lmbB2 of Streptomyces lincolnensis encode enzymes involved in the conversion of L-tyrosine to propylproline during the biosynthesis of the antibiotic lincomycin A. Arch. Microbiol. 169 (1998) 322-332. [PMID: 9531633]
2. Connor, K.L., Colabroy, K.L. and Gerratana, B. A heme peroxidase with a functional role as an L-tyrosine hydroxylase in the biosynthesis of anthramycin. Biochemistry 50 (2011) 8926-8936. [PMID: 21919439]
Accepted name: [1-hydroxy-2-(trimethylamino)ethyl]phosphonate dioxygenase (glycine-betaine-forming)
Reaction: [(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate + O2 = glycine betaine + phosphate
Other name(s): tmpB (gene name)
Systematic name: [(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate:oxygen 1R-oxidoreductase (glycine-betaine-forming)
Comments: Requires Fe2+. This bacterial enzyme is involved in a degradation pathway for [2-(trimethylamino)ethyl]phosphonate.
References:
1. Rajakovich, L.J., Pandelia, M.E., Mitchell, A.J., Chang, W.C., Zhang, B., Boal, A.K., Krebs, C. and Bollinger, J.M., Jr. A new microbial pathway for organophosphonate degradation catalyzed by two previously misannotated non-heme-iron oxygenases. Biochemistry 58 (2019) 1627-1647. [PMID: 30789718]
Accepted name: [2-(trimethylamino)ethyl]phosphonate dioxygenase
Reaction: [2-(trimethylamino)ethyl]phosphonate + 2-oxoglutarate + O2 = [(1R)-1-hydroxy-2-(trimethylamino)ethyl]phosphonate + succinate + CO2
Other name(s): tmpA (gene name)
Systematic name: [2-(trimethylamino)ethyl]phosphonate,2-oxoglutarate:oxygen oxidoreductase (1R-hydroxylating)
Comments: Requires Fe2+ and ascorbate. The enzyme, found in bacteria, participates in a degradation pathway for [2-(trimethylamino)ethyl]phosphonate.
References:
1. Rajakovich, L.J., Pandelia, M.E., Mitchell, A.J., Chang, W.C., Zhang, B., Boal, A.K., Krebs, C. and Bollinger, J.M., Jr. A new microbial pathway for organophosphonate degradation catalyzed by two previously misannotated non-heme-iron oxygenases. Biochemistry 58 (2019) 1627-1647. [PMID: 30789718]
Accepted name: 3,5,6-trichloropyridin-2-ol monooxygenase
Reaction: (1) 3,5,6-trichloropyridin-2-ol + FADH2 + O2 = 3,6-dichloropyridine-2,5-dione + Cl- + FAD + H2O
(2) 3,6-dichloropyridine-2,5-diol + FADH2 + O2 = 6-chloro-3-hydroxypyridine-2,5-dione + Cl- + FAD + H2O
(3) 6-chloropyridine-2,3,5-triol + FADH2 + O2 = 3,6-dihydroxypyridine-2,5-dione + Cl- + FAD + H2O
Other name(s): tcpA (gene name)
Systematic name: 3,5,6-trichloropyridin-2-ol,FADH2:oxygen oxidoreductase (dechlorinating)
Comments: The enzyme, characterized from a number of bacterial species, participates in the degradation of 3,5,6-trichloropyridin-2-ol (TCP), a metabolite of the common organophosphorus insecticide chlorpyrifos. The enzyme is a multifunctional flavin-dependent monooxygenase that displaces three chlorine atoms by attacking three different positions in the substrate. Each reaction catalysed by the enzyme displaces a single chlorine and results in formation of a dione, which must be reduced by FADH2 before the monooxygenase could catalyse the next step. The large amount of FADH2 that is required is generated by a dedicated flavin reductase (TcpX). cf. EC 1.14.14.173, 2,4,6-trichlorophenol monooxygenase.
References:
1. Li, J., Huang, Y., Hou, Y., Li, X., Cao, H. and Cui, Z. Novel gene clusters and metabolic pathway involved in 3,5,6-trichloro-2-pyridinol degradation by Ralstonia sp. strain T6. Appl. Environ. Microbiol. 79 (2013) 7445-7453. [PMID: 24056464]
2. Fang, L., Shi, T., Chen, Y., Wu, X., Zhang, C., Tang, X., Li, Q.X. and Hua, R. Kinetics and catabolic pathways of the insecticide chlorpyrifos, annotation of the degradation genes, and characterization of enzymes TcpA and Fre in Cupriavidus nantongensis X1(T). J. Agric. Food Chem. 67 (2019) 2245-2254. [PMID: 30721044]
Accepted name: 2,4,6-trichlorophenol monooxygenase
Reaction: (1) 2,4,6-trichlorophenol + FADH2 + O2 = 2,6-dichlorobenzoquinone + Cl- + FAD + H2O
(2) 2,6-dichlorohydroquinone + FADH2 + O2 = 2-chloro-6-hydroxy-1,4-benzoquinone + Cl- + FAD + H2O
Other name(s): tcpA (gene name)
Systematic name: 2,4,6-trichlorophenol,FADH2:oxygen oxidoreductase (dechlorinating)
Comments: The enzyme, characterized from a number of bacterial species, participates in the degradation of 2,4,6-trichlorophenol, a compound that has been used for decades as a wood preservative. The enzyme is a multifunctional flavin-dependent monooxygenase that displaces two chlorine atoms by attacking two different positions in the substrate. Each reaction catalysed by the enzyme displaces a single chlorine and results in formation of a dione, which must be reduced by FADH2 before the monooxygenase could catalyse the second reaction. The large amount of FADH2 that is required is generated by a dedicated flavin reductase (TcpB). cf. EC 1.14.14.172, 3,5,6-trichloropyridin-2-ol monooxygenase.
References:
1. Louie, T.M., Webster, C.M. and Xun, L. Genetic and biochemical characterization of a 2,4,6-trichlorophenol degradation pathway in Ralstonia eutropha JMP134. J. Bacteriol. 184 (2002) 3492-3500. [PMID: 12057943]
[EC 1.14.16.3 Deleted entry: anthranilate 3-monooxygenase. Withdrawn due to insufficient evidence. (EC 1.14.16.3 created 1972, deleted 2020)]
Accepted name: plasmanylethanolamine desaturase
Reaction: a plasmanylethanolamine + 2 ferrocytochrome b5 + O2 + 2 H+ = a plasmenylethanolamine + 2 ferricytochrome b5 + 2 H2O
Glossary: a plasmanylethanolamine = a 2-acyl-1-alkyl-sn-glycero-3-phosphoethanolamine
Other name(s): TMEM189 (gene name); 2-acyl-1-alkyl-sn-glycero-3-phosphoethanolamine desaturase; alkylacylglycerophosphoethanolamine desaturase; alkylacylglycero-phosphorylethanolamine dehydrogenase; alkyl-acylglycerophosphorylethanolamine dehydrogenase; 1-O-alkyl-2-acyl-sn-glycero-3-phosphorylethanolamine desaturase; 1-O-alkyl 2-acyl-sn-glycero-3-phosphorylethanolamine desaturase
Systematic name: plasmanylethanolamine,ferrocytochrome b5:oxygen oxidoreductase (plasmenylethanolamine-forming)
Comments: The enzyme catalyses the introduction of a double bond at position 1 of the alkyl group attached by an ether bond at the sn-1 position of plasmanylethanolamine, generating a vinyl ether-containing plasmenylethanolamine. The enzyme is found in animals and some bacteria, but not in plants, fungi, or most aerobic bacteria.
References:
1. Stoffel, W. and LeKim, D. Studies on the biosynthesis of plasmalogens. Precursors in the biosynthesis of plasmalogens: on the stereospecificity of the biochemical dehydrogenation of the 1-O-alkyl glyceryl to the 1-O-alk-1'-enyl glyceryl ether bond. Hoppe-Seylers Z. Physiol. Chem. 352 (1971) 501-511. [PMID: 5550967]
2. Paltauf, F. Biosynthesis of plasmalogens from alkyl- and alkyl-acyl-glycerophosphoryl ethanolamine in the rat brain. FEBS Lett. 17 (1971) 118-120. [PMID: 11946011]
3. Paltuaf, F., Prough, R.A., Masters, B.S. and Johnston, J.M. Evidence for the participation of cytochrome b5 in plasmalogen biosynthesis. J. Biol. Chem. 249 (1974) 2661-2662. [PMID: 4150797]
4. Wykle, R.L. and Schremmer Lockmiller, J.M. The biosynthesis of plasmalogens by rat brain: involvement of the microsomal electron transport system. Biochim. Biophys. Acta 380 (1975) 291-298. [PMID: 235322]
5. Gallego-Garcia, A., Monera-Girona, A.J., Pajares-Martinez, E., Bastida-Martinez, E., Perez-Castano, R., Iniesta, A.A., Fontes, M., Padmanabhan, S. and Elias-Arnanz, M. A bacterial light response reveals an orphan desaturase for human plasmalogen synthesis. Science 366 (2019) 128-132. [PMID: 31604315]
[EC 1.14.99.19 Transferred entry: plasmanylethanolamine desaturase. Now classified as EC 1.14.19.77, plasmanylethanolamine desaturase (EC 1.14.99.19 created 1976, deleted 2020)]
[EC 1.16.1.3 Deleted entry: aquacobalamin reductase. This entry has been deleted since no specific enzyme catalysing this activity has been identified and it has been shown that aquacobalamin is efficiently reduced by free dihydroflavins and by non-specific reduced flavoproteins. (EC 1.16.1.3 created 1972 as EC 1.6.99.8, transferred 2002 to EC 1.16.1.3, modified 2020, deleted 2020)]
[EC 1.16.1.5 Deleted entry: aquacobalamin reductase (NADPH). This entry has been deleted since the enzyme the entry was based on was later shown to be EC 1.2.1.51, pyruvate dehydrogenase (NADP+). On the other hand, it has been shown that non-enzymatic reduction of cob(III)alamin to cob(II)alamin occurs efficiently in the presence of free dihydroflavins or non-specific reduced flavoproteins. (EC 1.16.1.5 created 1989 as EC 1.6.99.11, transferred 2002 to EC 1.16.1.5, modified 2020, deleted 2020)]
Accepted name: [histone H3]-lysine4 N-trimethyltransferase
Reaction: 3 S-adenosyl-L-methionine + a [histone H3]-L-lysine4 = 3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4 (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine4 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine4
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine4 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine4
(1c) S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine4 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
Other name(s): KMT2A (gene name); KMT2B (gene name); KMT2C (gene name); KMT2D (gene name); KMT2F (gene name); KMT2G (gene name); KMT2H (gene name); KMT3C (gene name); KMT3D (gene name); KMT3E (gene name); PRDM9 (gene name); MLL1 (gene name); MLL2 (gene name); MLL3 (gene name); MLL4 (gene name); MLL5 (gene name); SETD1A (gene name); ASH1L (gene name); SMYD1 (gene name); SMYD2 (gene name); SMYD3 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine4 N6-trimethyltransferase
Comments: This entry describes several enzymes that successively methylate the L-lysine4 residue of histone H3 (H3K4), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. In most cases the trimethylation of this position is associated with gene activation. EC 2.1.1.364, [histone H3]-lysine4 N-methyltransferase, describes enzymes that can catalyse only monomethylation of this substrate (the first sub-reaction of this entry).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1. Nakamura, T., Mori, T., Tada, S., Krajewski, W., Rozovskaia, T., Wassell, R., Dubois, G., Mazo, A., Croce, C.M. and Canaani, E. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol. Cell 10 (2002) 1119-1128. [PMID: 12453419]
2. Hamamoto, R., Furukawa, Y., Morita, M., Iimura, Y., Silva, F.P., Li, M., Yagyu, R. and Nakamura, Y. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat. Cell Biol. 6 (2004) 731-740. [PMID: 15235609]
3. Blazer, L.L., Lima-Fernandes, E., Gibson, E., Eram, M.S., Loppnau, P., Arrowsmith, C.H., Schapira, M. and Vedadi, M. PR domain-containing protein 7 (PRDM7) is a histone 3 lysine 4 trimethyltransferase. J. Biol. Chem. 291 (2016) 13509-13519. [PMID: 27129774]
Accepted name: [histone H3]-lysine4 N-methyltransferase
Reaction: S-adenosyl-L-methionine + a [histone H3]-L-lysine4 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine4
Other name(s): KMT7 (gene name); SETD7 (gene name); SET7/9 (gene name); KIAA1717 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine4 N6-methyltransferase
Comments: This entry describes enzymes that catalyse a single methylation of the L-lysine4 residue of histone H3 (H3K4), generating a monomethylated form. This modifications influence the binding of chromatin-associated proteins and result in gene activation or suppression. Some enzymes that catalyse this reaction continue to generate a trimethylated form; these enzymes are classified under EC 2.1.1.354, [histone H3]-lysine4 N-trimethyltransferase.
References:
1. Wang, H., Cao, R., Xia, L., Erdjument-Bromage, H., Borchers, C., Tempst, P. and Zhang, Y. Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol. Cell 8 (2001) 1207-1217. [PMID: 11779497]
2. Nishioka, K., Chuikov, S., Sarma, K., Erdjument-Bromage, H., Allis, C.D., Tempst, P. and Reinberg, D. Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev. 16 (2002) 479-489. [PMID: 11850410]
3. Wilson, J.R., Jing, C., Walker, P.A., Martin, S.R., Howell, S.A., Blackburn, G.M., Gamblin, S.J. and Xiao, B. Crystal structure and functional analysis of the histone methyltransferase SET7/9. Cell 111 (2002) 105-115. [PMID: 12372304]
4. Xiao, B., Jing, C., Wilson, J.R., Walker, P.A., Vasisht, N., Kelly, G., Howell, S., Taylor, I.A., Blackburn, G.M. and Gamblin, S.J. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature 421 (2003) 652-656. [PMID: 12540855]
5. Hu, P. and Zhang, Y. Catalytic mechanism and product specificity of the histone lysine methyltransferase SET7/9: an ab initio QM/MM-FE study with multiple initial structures. J. Am. Chem. Soc. 128 (2006) 1272-1278. [PMID: 16433545]
Accepted name: MMP 1-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3,3'-di-O-methyl-4α-mannobiose = S-adenosyl-L-homocysteine + 1,3,3'-tri-O-methyl-4α-mannobiose
Glossary: 3,3'-di-O-methyl-4α-mannobiose = 3-O-methyl-α-D-mannopyranosyl-(1→4)-3-O-methyl-α-D-mannopyranose
Other name(s): MeT1; 3-O-methylmannose polysaccharide 1-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:3,3'-di-O-methyl-4α-mannobiose 1-O-methyltransferase
Comments: Requires Mg2+. The enzyme, characterized from the bacterium Mycolicibacterium hassiacum, participates in the biosynthesis of 3-O-methylmannose polysaccharides (MMP), which are intracellular polymethylated polysaccharides implicated in the modulation of fatty acid metabolism in nontuberculous mycobacteria. The methylation catalysed by this enzyme was shown to block the reducing end of 3,3'-di-O-methyl-α-mannobiose, a probable early precursor of the 3-O-methylmannose polysaccharides.
References:
1. Ripoll-Rozada, J., Costa, M., Manso, J.A., Maranha, A., Miranda, V., Sequeira, A., Ventura, M.R., Macedo-Ribeiro, S., Pereira, P.JB. and Empadinhas, N. Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides. Proc. Natl. Acad. Sci. USA 116 (2019) 835-844. [PMID: 30606802]
Accepted name: E2 NEDD8-conjugating enzyme
Reaction: [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine + [E2 NEDD8-conjugating enzyme]-L-cysteine = [E1 NEDD8-activating enzyme]-L-cysteine + [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine
Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein
Other name(s): NEDD8-carrier-protein E2; NEDD8-conjugating enzyme E2; UBE2M (gene name); UBE2F (gene name)
Systematic name: [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine:[E2 NEDD8-conjugating enzyme] [NEDD8-protein]-yl transferase
Comments: Some RING-type E3 ubiquitin transferases (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form complexes with a cullin scaffold protein and a substrate recognition module, which are known as CRL (Cullin-RING-Ligase) complexes. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. Like ubiquitin, the NEDD8 protein ends with two glycine residues. EC 6.2.1.64, E1 NEDD8-activating enzyme, activates NEDD8 in an ATP-dependent reaction by forming a high-energy thioester intermediate between NEDD8 and one of its cysteine residues. The activated NEDD8 is subsequently transferred to a cysteine residue of an E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase).
References:
1. Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K. and Kato, S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 12 (1998) 2263-2268. [PMID: 9694792]
2. Gong, L. and Yeh, E.T. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J. Biol. Chem. 274 (1999) 12036-12042. [PMID: 10207026]
3. Huang, D.T., Miller, D.W., Mathew, R., Cassell, R., Holton, J.M., Roussel, M.F. and Schulman, B.A. A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat. Struct. Mol. Biol. 11 (2004) 927-935. [PMID: 15361859]
4. Huang, D.T., Ayrault, O., Hunt, H.W., Taherbhoy, A.M., Duda, D.M., Scott, D.C., Borg, L.A., Neale, G., Murray, P.J., Roussel, M.F. and Schulman, B.A. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol. Cell 33 (2009) 483-495. [PMID: 19250909]
Accepted name: capsaicin synthase
Reaction: (6E)-8-methylnon-6-enoyl-CoA + vanillylamine = CoA + capsaicin
Other name(s): CS (gene name) (ambiguous); Pun1 (locus name)
Systematic name: (6E)-8-methylnon-6-enoyl-CoA:vanillylamine 8-methylnon-6-enoyltranferase
Comments: The enzyme, found only in plants that belong to the Capsicum genus, catalyses the last step in the biosynthesis of capsaicinoids. The enzyme catalyses the acylation of vanillylamine by a branched-chain fatty acid. The exact structure of the fatty acid determines the type of capsaicinoid formed.
References:
1. Blum, E., Liu, K., Mazourek, M., Yoo, E.Y., Jahn, M. and Paran, I. Molecular mapping of the C locus for presence of pungency in Capsicum. Genome 45 (2002) 702-705. [PMID: 12175073]
2. Stewart, C., Jr., Kang, B.C., Liu, K., Mazourek, M., Moore, S.L., Yoo, E.Y., Kim, B.D., Paran, I. and Jahn, M.M. The Pun1 gene for pungency in pepper encodes a putative acyltransferase. Plant J. 42 (2005) 675-688. [PMID: 15918882]
3. Kim, S., Park, M., Yeom, S.I., Kim, Y.M., Lee, J.M., Lee, H.A., Seo, E., Choi, J., Cheong, K., Kim, K.T., Jung, K., Lee, G.W., Oh, S.K., Bae, C., Kim, S.B., Lee, H.Y., Kim, S.Y., Kim, M.S., Kang, B.C., Jo, Y.D., Yang, H.B., Jeong, H.J., Kang, W.H., Kwon, J.K., Shin, C., Lim, J.Y., Park, J.H., Huh, J.H., Kim, J.S., Kim, B.D., Cohen, O., Paran, I., Suh, M.C., Lee, S.B., Kim, Y.K., Shin, Y., Noh, S.J., Park, J., Seo, Y.S., Kwon, S.Y., Kim, H.A., Park, J.M., Kim, H.J., Choi, S.B., Bosland, P.W., Reeves, G., Jo, S.H., Lee, B.W., Cho, H.T., Choi, H.S., Lee, M.S., Yu, Y., Do Choi, Y., Park, B.S., van Deynze, A., Ashrafi, H., Hill, T., Kim, W.T., Pai, H.S., Ahn, H.K., Yeam, I., Giovannoni, J.J., Rose, J.K., Sorensen, I., Lee, S.J., Kim, R.W., Choi, I.Y., Choi, B.S., Lim, J.S., Lee, Y.H. and Choi, D. Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species. Nat. Genet. 46 (2014) 270-278. [PMID: 24441736]
Accepted name: rhamnogalacturonan I galactosyltransferase
Reaction: Transfer of a β-galactosyl residue in a β-(1→4) linkage from UDP-α-D-galactose to rhamnosyl residues within the rhamnogalacturonan I backbone.
Glossary: rhamnogalacturonan I backbone = [(1→2)-α-L-rhamnosyl-(1→4)-α-D-galacturonosyl]n
Systematic name: UDP-α-D-galactose:[rhamnogalacturonan I]-α-L-rhamnosyl β-1,4-galactosyltransferase (configuration-inverting)
Comments: The enzyme, characterized from the plant Vigna angularis (azuki beans), participates in the biosynthesis of rhamnogalacturonan I, one of the components of pectin in plant cell wall. It does not require any metal ions, and prefers substrates with a degree of polymerization larger than 9.
References:
1. Matsumoto, N., Takenaka, Y., Wachananawat, B., Kajiura, H., Imai, T. and Ishimizu, T. Rhamnogalacturonan I galactosyltransferase: Detection of enzyme activity and its hyperactivation. Plant Physiol. Biochem. 142 (2019) S0981-9428(. [PMID: 31299599]
Accepted name: EGF-domain serine glucosyltransferase
Reaction: UDP-α-D-glucose + [protein with EGF-like domain]-L-serine = UDP + [protein with EGF-like domain]-3-O-(β-D-glucosyl)-L-serine
Other name(s): POGLUT1 (gene name) (ambiguous); rumi (gene name) (ambiguous)
Systematic name: UDP-α-D-glucose:[protein with EGF-like domain]-L-serine O-β-glucosyltransferase (configuration-inverting)
Comments: The enzyme, found in animals and insects, is involved in the biosynthesis of the α-D-xylosyl-(1→3)-α-D-xylosyl-(1→3)-β-D-glucosyl trisaccharide on epidermal growth factor-like (EGF-like) domains. Glycosylation takes place at the serine in the C-X-S-X-P-C motif. The enzyme is bifunctional also being active with UDP-α-xylose as donor (EC 2.4.2.63, EGF-domain serine xylosyltransferase). When present on Notch proteins, the trisaccharide functions as a modulator of the signalling activity of this protein.
References:
1. Li, Z., Fischer, M., Satkunarajah, M., Zhou, D., Withers, S.G. and Rini, J.M. Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1). Nat. Commun. 8 (2017) 185. [PMID: 28775322]
Accepted name: xylosyl α-1,3-xylosyltransferase
Reaction: UDP-α-D-xylose + [protein with EGF-like domain]-3-O-[α-D-xylosyl-(1→3)-β-D-glucosyl]-L-serine = UDP + [protein with EGF-like domain]-3-O-[α-D-xylosyl-(1→3)-α-D-xylosyl-(1→3)-β-D-glucosyl]-L-serine
Other name(s): XXYLT1 (gene name)
Systematic name: UDP-α-D-xylose:[EGF-like domain protein]-3-O-[α-D-xylosyl-(1→3)-β-D-glucosyl]-L-serine 3-α-D-xylosyltransferase (configuration-retaining)
Comments: The enzyme, found in animals and insects, is involved in the biosynthesis of the α-D-xylosyl-(1→3)-α-D-xylosyl-(1→3)-β-D-glucosyl trisaccharide on epidermal growth factor-like (EGF-like) domains. When present on Notch proteins, the trisaccharide functions as a modulator of the signalling activity of this protein.
References:
1. Minamida, S., Aoki, K., Natsuka, S., Omichi, K., Fukase, K., Kusumoto, S. and Hase, S. Detection of UDP-D-xylose: α-D-xyloside α 1-→3xylosyltransferase activity in human hepatoma cell line HepG2. J. Biochem. 120 (1996) 1002-1006. [PMID: 8982869]
2. Sethi, M.K., Buettner, F.F., Ashikov, A., Krylov, V.B., Takeuchi, H., Nifantiev, N.E., Haltiwanger, R.S., Gerardy-Schahn, R. and Bakker, H. Molecular cloning of a xylosyltransferase that transfers the second xylose to O-glucosylated epidermal growth factor repeats of notch. J. Biol. Chem. 287 (2012) 2739-2748. [PMID: 22117070]
3. Yu, H., Takeuchi, M., LeBarron, J., Kantharia, J., London, E., Bakker, H., Haltiwanger, R.S., Li, H. and Takeuchi, H. Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism. Nat. Chem. Biol. 11 (2015) 847-854. [PMID: 26414444]
Accepted name: EGF-domain serine xylosyltransferase
Reaction: UDP-α-D-xylose + [protein with EGF-like domain]-L-serine = UDP + [protein with EGF-like domain]-3-O-(β-D-xylosyl)-L-serine
Other name(s): POGLUT1 (gene name) (ambiguous); rumi (gene name) (ambiguous)
Systematic name: UDP-α-D-xylose:[protein with EGF-like domain]-L-serine O-β-xylosyltransferase (configuration-inverting)
Comments: The enzyme, found in animals and insects, xylosylates at the serine in the C-X-S-X-P-C motif of epidermal growth factor-like (EGF-like) domains. The enzyme is bifunctional also being active with UDP-α-glucose as donor (EC 2.4.1.376, EGF-domain serine glucosyltransferase).
References:
1. Li, Z., Fischer, M., Satkunarajah, M., Zhou, D., Withers, S.G. and Rini, J.M. Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1). Nat. Commun. 8 (2017) 185. [PMID: 28775322]
Accepted name: N-acetylglucosaminide α-(2,6)-sialyltransferase
Reaction: CMP-N-acetyl-β-neuraminate + N-acetyl-α-neuraminyl-(2→3)-β-D-galactosyl-(1→3)-N-acetyl-β-D-glucosaminyl-R = CMP + N-acetyl-α-neuraminyl-(2→3)-β-D-galactosyl-(1→3)-[N-acetyl-α-neuraminyl-(2→6)]-N-acetyl-β-D-glucosaminyl-R
Other name(s): α-N-acetylneuraminyl-2,3-β-galactosyl-1,3-N-acetylglucosaminide 6-α-sialyltransferase; N-acetylglucosaminide (α 2→6)-sialyltransferase; ST6GlcNAc
Systematic name: CMP-N-acetylneuraminate:N-acetyl-α-neuraminyl-(2→3)-β-D-galactosyl-(1→3)-N-acetyl-β-D-glucosaminide N-acetyl-β-D-glucosamine-6-α-N-acetylneuraminyltransferase (configuration-inverting)
Comments: Attaches N-acetylneuraminic acid in α-2,6-linkage to N-acetyl-β-D-glucosamine. The enzyme from rat liver also acts on β-D-galactosyl-(1→3)-N-acetyl-β-D-glucosaminyl residues, but more slowly.
References:
1. Paulson, J.C., Weinstein, J. and de Souza-e-Silva, U. Biosynthesis of a disialylated sequence in N-linked oligosaccharides: identification of an N-acetylglucosaminide (α 2→6)-sialyltransferase in Golgi apparatus from rat liver. Eur. J. Biochem. 140 (1984) 523-530. [PMID: 6547092]
Accepted name: 4-hydroxyglutamate transaminase
Reaction: erythro-4-hydroxy-L-glutamate + 2-oxoglutarate = (4R)-4-hydroxy-2-oxoglutarate + L-glutamate
For diagram of reaction, click here and for mechanism, click here
Glossary: erythro-4-hydroxy-L-glutamate = (2S,4R)-2-amino-4-hydroxypentanedioate
Other name(s): 4-hydroxyglutamate aminotransferase; 4-hydroxy-L-glutamate:2-oxoglutarate aminotransferase
Systematic name: erythro-4-hydroxy-L-glutamate:2-oxoglutarate aminotransferase
Comments: The enzyme participates in a degradation pathway of trans-4-hydroxy-L-proline, a compound that contributes to the stability of the collagen triple helix. Oxaloacetate can replace 2-oxoglutarate. This enzyme may be identical with EC 2.6.1.1 aspartate transaminase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 37277-86-4
References:
1. Goldstone, A. and Adams, E. Metabolism of γ-hydroxyglutamic acid. I. Conversion to α-hydroxy-γ-ketoglutarate by purified glutamic-aspartic transaminase to rat liver. J. Biol. Chem. 237 (1962) 3476-3485. [PMID: 13948827]
2. Kuratomi, K., Fukunaga, K. and Kobayashi, Y. The metabolism of γ-hydroxyglutamate in rat liver. II. A transaminase concerned in γ-hydroxyglutamate metabolism. Biochim. Biophys. Acta 78 (1963) 629-636. [PMID: 14089443]
3. Maitra U, Deekker E Purification of rat-liver γ-hydroxyglutamate transaminase and its probable identity with glutamate-aspartate transaminase. Biochim. Biophys. Acta 81 (1964) 517-532. [PMID: 14170323]
Accepted name: vanillin aminotransferase
Reaction: L-alanine + vanillin = pyruvate + vanillylamine
Other name(s): VAMT (gene name)
Systematic name: L-alanine:vanillin aminotransferase
Comments: The enzyme participates in the biosynthesis of capsaicinoids in pungent cultivars of Capsicum sp. In vivo it has only been assayed in the reverse direction, where the preferred amino group acceptors were found to be pyruvate and oxaloacetate.
References:
1. Curry, J., Aluru, M., Mendoza, M., Nevarez, J., Melendrez, M. and O'Connell, M.A. Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum spp. Plant Sci. 148 (1999) 47-57.
2. del Rosario Abraham-Juarez, M., del Carmen Rocha-Granados, M., Lopez, M.G., Rivera-Bustamante, R.F. and Ochoa-Alejo, N. Virus-induced silencing of Comt, pAmt and Kas genes results in a reduction of capsaicinoid accumulation in chili pepper fruits. Planta 227 (2008) 681-695. [PMID: 17999078]
3. Lang, Y., Kisaka, H., Sugiyama, R., Nomura, K., Morita, A., Watanabe, T., Tanaka, Y., Yazawa, S. and Miwa, T. Functional loss of pAMT results in biosynthesis of capsinoids, capsaicinoid analogs, in Capsicum annuum cv. CH-19 Sweet. Plant J. 59 (2009) 953-961. [PMID: 19473323]
4. Gururaj, H.B., Padma, M.N., Giridhar, P. and Ravishankar, G.A. Functional validation of Capsicum frutescens aminotransferase gene involved in vanillylamine biosynthesis using Agrobacterium mediated genetic transformation studies in Nicotiana tabacum and Capsicum frutescens calli cultures. Plant Sci. 195 (2012) 96-105. [PMID: 22921003]
5. Weber, N., Ismail, A., Gorwa-Grauslund, M. and Carlquist, M. Biocatalytic potential of vanillin aminotransferase from Capsicum chinense. BMC Biotechnol 14 (2014) 25. [PMID: 24712445]
Accepted name: uridine/cytidine kinase
Reaction: (1) ATP + uridine = ADP + UMP
(2) ATP + cytidine = ADP + CMP
Other name(s): UCK (gene name); URK1 (gene name); pyrimidine ribonucleoside kinase; uridine-cytidine kinase; uridine kinase (phosphorylating); uridine phosphokinase; ATP:uridine 5'-phosphotransferase; uridine kinase
Systematic name: ATP:uridine/cytidine 5'-phosphotransferase
Comments: The enzyme, found in prokaryotes and eukaryotes, phosphorylates both uridine and cytidine to their monophosphate forms. The enzyme from Escherichia coli prefers GTP to ATP. The human enzyme also catalyses the phosphorylation of several cytotoxic ribonucleoside analogs. cf. EC 2.7.1.213, cytidine kinase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9026-39-5
References:
1. Sköld, O. Uridine kinase from Erlich ascites tumor: purification and properties. J. Biol. Chem. 235 (1960) 3273-3279.
2. Orengo, A. Regulation of enzymic activity by metabolites. I. Uridine-cytidine kinase of Novikoff ascites rat tumor. J. Biol. Chem. 244 (1969) 2204-2209. [PMID: 5782006]
3. Valentin-Hansen, P. Uridine-cytidine kinase from Escherichia coli. Methods Enzymol. 51 (1978) 308-314. [PMID: 211379]
4. Kern, L. The URK1 gene of Saccharomyces cerevisiae encoding uridine kinase. Nucleic Acids Res. 18 (1990) 5279. [PMID: 2169608]
5. Van Rompay, A.R., Norda, A., Linden, K., Johansson, M. and Karlsson, A. Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases. Mol. Pharmacol. 59 (2001) 1181-1186. [PMID: 11306702]
6. Ohler, L., Niopek-Witz, S., Mainguet, S.E. and Mohlmann, T. Pyrimidine salvage: physiological functions and interaction with chloroplast biogenesis. Plant Physiol. 180 (2019) 1816-1828. [PMID: 31101721]
Accepted name: 3-oxoisoapionate kinase
Reaction: ATP + 3-oxoisoapionate = ADP + 3-oxoisoapionate 4-phosphate
Glossary: 3-oxoisoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate
Other name(s): oiaK (gene name)
Systematic name: ATP:3-oxoisoapionate 4-phosphotransferase
Comments: The enzyme, characterized from several bacterial species, participates in the degradation of D-apionate. Stereospecificity of the product, 3-oxoisoapionate 4-phosphate, has not been determined.
References:
1. Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696-705. [PMID: 29867142]
[EC 2.7.2.13 Deleted entry: , now known to be due to the activities of EC 6.1.1.17, glutamate---tRNA ligase, EC 1.2.1.70, glutamyl-tRNA reductase and EC 5.4.3.8, glutamate-1-semialdehyde 2,1-aminomutase (EC 2.7.2.13 created 1984, deleted 2020)]
Accepted name: AMP-polyphosphate phosphotransferase
Reaction: ADP + (phosphate)n = AMP + (phosphate)n+1
Other name(s): PA3455 (locus name); PPK2D; PAP
Systematic name: ADP:polyphosphate phosphotransferase
Comments: The enzyme, characterized from the bacteria Acinetobacter johnsonii and Pseudomonas aeruginosa, transfers a phosphate group from polyphosphates to nucleotide monophosphates. The highest activity is achieved with AMP, but the enzyme can also phosphorylate GMP, dAMP, dGMP, IMP, and XMP. The reverse reactions were not detected.
References:
1. Bonting, C.F., Kortstee, G.J. and Zehnder, A.J. Properties of polyphosphate: AMP phosphotransferase of Acinetobacter strain 210A. J. Bacteriol. 173 (1991) 6484-6488. [PMID: 1655714]
2. Shiba, T., Itoh, H., Kameda, A., Kobayashi, K., Kawazoe, Y. and Noguchi, T. Polyphosphate:AMP phosphotransferase as a polyphosphate-dependent nucleoside monophosphate kinase in Acinetobacter johnsonii 210A. J. Bacteriol. 187 (2005) 1859-1865. [PMID: 15716459]
3. Nocek, B., Kochinyan, S., Proudfoot, M., Brown, G., Evdokimova, E., Osipiuk, J., Edwards, A.M., Savchenko, A., Joachimiak, A. and Yakunin, A.F. Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria. Proc. Natl. Acad. Sci. USA 105 (2008) 17730-17735. [PMID: 19001261]
Accepted name: 2-hydroxyethylphosphonate cytidylyltransferase
Reaction: 2-hydroxyethylphosphonate + CTP = cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + diphosphate
Other name(s): Fom1
Systematic name: CTP:2-hydroxyethylphosphonate cytidylyltransferase
Comments: The enzyme, isolated from the bacterium Streptomyces wedmorensis, is involved in fosfomycin biosynthesis. The enzyme also is active as EC 5.4.2.9 phosphoenolpyruvate mutase.
References:
1. Cho, S.H., Kim, S.Y., Tomita, T., Shiraishi, T., Park, J.S., Sato, S., Kudo, F., Eguchi, T., Funa, N., Nishiyama, M. and Kuzuyama, T. Fosfomycin biosynthesis via transient cytidylylation of 2-hydroxyethylphosphonate by the bifunctional Fom1 enzyme. ACS Chem. Biol. 12 (2017) 2209-2215. [PMID: 28727444]
Accepted name: exo β-1,2-glucooligosaccharide sophorohydrolase (non-reducing end)
Reaction: [(1→2)-β-D-glucosyl]n + H2O = sophorose + [(1→2)-β-D-glucosyl]n-2
Glossary: sophorose = β-D-glucopyranosyl-(1→2)-D-glucopyranose
Systematic name: exo (1→2)-β-D-glucooligosaccharide sophorohydrolase (non-reducing end)
Comments: The enzyme, characterized from the bacterium Parabacteroides distasonis, specifically hydrolyses (1→2)-β-D-glucooligosaccharides to sophorose. The best substrates are the tetra- and pentasaccharides. The enzyme is not able to cleave the trisaccharide, and activity with longer linear (1→2)-β-D-glucans is quite low. This enzyme acts in exo mode and is not able to hydrolyse cyclic (1→2)-β-D-glucans.
References:
1. Shimizu, H., Nakajima, M., Miyanaga, A., Takahashi, Y., Tanaka, N., Kobayashi, K., Sugimoto, N., Nakai, H. and Taguchi, H. Characterization and structural analysis of a novel exo-type enzyme acting on β-1,2-glucooligosaccharides from Parabacteroides distasonis. Biochemistry 57 (2018) 3849-3860. [PMID: 29763309]
Accepted name: adenosylhomocysteine nucleosidase
Reaction: (1) S-adenosyl-L-homocysteine + H2O = S-(5-deoxy-D-ribos-5-yl)-L-homocysteine + adenine
(2) 5'-deoxyadenosine + H2O = 5-deoxy-D-ribose + adenine
(3) S-methyl-5'-thioadenosine + H2O = 5-(methylsulfanyl)-D-ribose + adenine
For diagram of autoinducer AI-2 biosynthesis, click here and for diagram of the methionine-salvage pathway, click here
Other name(s): S-adenosylhomocysteine hydrolase (ambiguous); S-adenosylhomocysteine nucleosidase; 5'-methyladenosine nucleosidase; S-adenosylhomocysteine/5'-methylthioadenosine nucleosidase; AdoHcy/MTA nucleosidase; MTN2 (gene name); mtnN (gene name)
Systematic name: S-adenosyl-L-homocysteine homocysteinylribohydrolase
Comments: This enzyme, found in bacteria and plants, acts on three different substrates. It is involved in the S-adenosyl-L-methionine (SAM, AdoMet) cycle, which recycles S-adenosyl-L-homocysteine back to SAM, and in salvage pathways for 5'-deoxyadenosine and S-methyl-5'-thioadenosine, which are produced from SAM during the action of many enzymes. cf. the plant enzyme EC 3.2.2.16, methylthioadenosine nucleosidase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9055-10-1
References:
1. Duerre, J.A. A hydrolytic nucleosidase acting on S-adenosylhomocysteine and on 5-methylthioadenosine. J. Biol. Chem. 237 (1962) 3737-3741.
2. Ferro, A.J., Barrett, A. and Shapiro, S.K. Kinetic properties and the effect of substrate analogues on 5'-methylthioadenosine nucleosidase from Escherichia coli. Biochim. Biophys. Acta 438 (1976) 487-494. [PMID: 782530]
3. Cornell, K.A., Swarts, W.E., Barry, R.D. and Riscoe, M.K. Characterization of recombinant Eschericha coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase: analysis of enzymatic activity and substrate specificity. Biochem. Biophys. Res. Commun. 228 (1996) 724-732. [PMID: 8941345]
4. Park, E.Y., Choi, W.S., Oh, S.I., Kim, K.N., Shin, J.S. and Song, H.K. Biochemical and structural characterization of 5'-methylthioadenosine nucleosidases from Arabidopsis thaliana. Biochem. Biophys. Res. Commun. 381 (2009) 619-624. [PMID: 19249293]
5. Farrar, C.E., Siu, K.K., Howell, P.L. and Jarrett, J.T. Biotin synthase exhibits burst kinetics and multiple turnovers in the absence of inhibition by products and product-related biomolecules. Biochemistry 49 (2010) 9985-9996. [PMID: 20961145]
6. North, J.A., Wildenthal, J.A., Erb, T.J., Evans, B.S., Byerly, K.M., Gerlt, J.A. and Tabita, F.R. A bifunctional salvage pathway for two distinct S-adenosylmethionine by-products that is widespread in bacteria, including pathogenic Escherichia coli. Mol. Microbiol. (2020) . [PMID: 31950558]
Accepted name: ureidoacrylate amidohydrolase
Reaction: (1) (Z)-3-ureidoacrylate + H2O = (Z)-3-aminoacrylate + CO2 + NH3 (overall reaction)
(1a) (Z)-3-ureidoacrylate + H2O = (Z)-3-aminoacrylate + carbamate
(1b) carbamate = CO2 + NH3 (spontaneous)
(2) (Z)-2-methylureidoacrylate + H2O = (Z)-2-methylaminoacrylate + CO2 + NH3 (overall reaction)
(2a) (Z)-2-methylureidoacrylate + H2O = (Z)-2-methylaminoacrylate + carbamate
(2b) carbamate = CO2 + NH3 (spontaneous)
Glossary: (Z)-3-ureidoacrylate = (2Z)-3-(carbamoylamino)prop-2-enoate
(Z)-2-methylureidoacrylate = (2Z)-3-(carbamoylamino)-2-methylprop-2-enoate
Other name(s): rutB (gene name)
Systematic name: (Z)-3-ureidoacrylate amidohydrolase
Comments: The enzyme participates in the Rut pyrimidine catabolic pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1. Kim, K.S., Pelton, J.G., Inwood, W.B., Andersen, U., Kustu, S. and Wemmer, D.E. The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems. J. Bacteriol. 192 (2010) 4089-4102. [PMID: 20400551]
Accepted name: N4-acetylcytidine amidohydrolase
Reaction: N4-acetylcytidine + H2O = cytidine + acetate
Other name(s): yqfB (gene name)
Systematic name: N4-acetylcytidine amidohydrolase
Comments: The enzyme from the bacterium Escherichia coli is one of the smallest known monomeric amidohydrolases (103-amino acids). The enzyme is active towards a wide range of N4-acylcytosines/cytidines, but is by far most active against N4-acetylcytidine.
References:
1. Shen, Y., Atreya, H.S., Liu, G. and Szyperski, T. G-matrix Fourier transform NOESY-based protocol for high-quality protein structure determination. J. Am. Chem. Soc. 127 (2005) 9085-9099. [PMID: 15969587]
2. Stanislauskiene, R., Laurynenas, A., Rutkiene, R., Aucynaite, A., Tauraite, D., Meskiene, R., Urbeliene, N., Kaupinis, A., Valius, M., Kaliniene, L. and Meskys, R. YqfB protein from Escherichia coli: an atypical amidohydrolase active towards N4-acylcytosine derivatives. Sci. Rep. 10 (2020) 788. [PMID: 31964920]
[EC 3.6.1.3 Deleted entry: adenosinetriphosphatase. Enzymes previously listed under this number are now listed separately under EC 5.6 and EC 7. (EC 3.6.1.3 created 1961 (EC 3.6.1.4 created 1961, incorporated 1965), deleted 2020)]
[EC 3.6.3.11 Deleted entry: Cl--transporting ATPase. The activity was only ever studied in crude extracts, and is an artifact. (EC 3.6.3.11 created 2000, deleted 2020)]
[EC 3.8.1.1 Deleted entry: alkylhalidase. Covered by EC 3.8.1.5, haloalkane dehalogenase. (EC 3.8.1.1 created 1961, deleted 2020)]
Accepted name: 3-oxoisoapionate decarboxylase
Reaction: 3-oxoisoapionate = L-erythrulose + CO2
Glossary: 3-oxoisoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate
Other name(s): oiaC (gene name)
Systematic name: 3-oxoisoapionate carboxy-lyase
Comments: The enzyme, characterized from several bacterial species, is involved in the degradation of D-apionate. Stereospecificity of 3-oxoisoapionate has not been determined.
References:
1. Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696-705. [PMID: 29867142]
Accepted name: 3-oxoisoapionate-4-phosphate decarboxylase
Reaction: 3-oxoisoapionate 4-phosphate = L-erythrulose 1-phosphate + CO2
Glossary: 3-oxoisoapionate = 2,4-dihydroxy-2-(hydroxymethyl)-3-oxobutanoate
Other name(s): oiaX (gene name)
Systematic name: 3-oxoisoapionate 4-phosphate carboxy-lyase
Comments: The enzyme, characterized from several bacterial species, participates in the degradation of D-apionate. It belongs to the RuBisCO-like-protein (RLP) superfamily. Stereospecificity of 3-oxoisoapionate 4-phosphate has not been determined.
References:
1. Carter, M.S., Zhang, X., Huang, H., Bouvier, J.T., Francisco, B.S., Vetting, M.W., Al-Obaidi, N., Bonanno, J.B., Ghosh, A., Zallot, R.G., Andersen, H.M., Almo, S.C. and Gerlt, J.A. Functional assignment of multiple catabolic pathways for D-apiose. Nat. Chem. Biol. 14 (2018) 696-705. [PMID: 29867142]
Accepted name: 5-deoxyribulose 1-phosphate aldolase
Reaction: (1) 5-deoxy-D-ribulose 1-phosphate = glycerone phosphate + acetaldehyde
(2) S-methyl-5-thio-D-ribulose 1-phosphate = glycerone phosphate + (2-methylsulfanyl)acetaldehyde
Other name(s): 5-(methylthio)ribulose-1-phosphate aldolase; ald2 (gene name)
Systematic name: 5-deoxy-D-ribulose 1-phosphate acetaldehyde-lyase (glycerone-phosphate-forming)
Comments: The enzyme, originally characterized from the bacterium Rhodospirillum rubrum, is involved in degradation pathways for 5'-deoxyadenosine and S-methyl-5'-thioadenosine, which are formed from S-adenosyl-L-methionine (SAM, AdoMet) by radical SAM enzymes and other types of SAM-dependent enzymes, respectively. The enzyme requires a divalent metal cation, with Co2+ producing the highest activity.
References:
1. North, J.A., Miller, A.R., Wildenthal, J.A., Young, S.J. and Tabita, F.R. Microbial pathway for anaerobic 5'-methylthioadenosine metabolism coupled to ethylene formation. Proc. Natl. Acad. Sci. USA 114 (2017) E10455-E10464. [PMID: 29133429]
2. North, J.A., Wildenthal, J.A., Erb, T.J., Evans, B.S., Byerly, K.M., Gerlt, J.A. and Tabita, F.R. A bifunctional salvage pathway for two distinct S-adenosylmethionine by-products that is widespread in bacteria, including pathogenic Escherichia coli. Mol. Microbiol. (2020) . [PMID: 31950558]
Accepted name: sirohydrochlorin cobaltochelatase
Reaction: cobalt-sirohydrochlorin + 2 H+ = sirohydrochlorin + Co2+
For diagram of corrin and siroheme biosynthesis (part 2), click here
Other name(s): CbiK; CbiX; CbiXS; anaerobic cobalt chelatase; cobaltochelatase [ambiguous]; sirohydrochlorin cobalt-lyase
Systematic name: cobalt-sirohydrochlorin cobalt-lyase (sirohydrochlorin-forming)
Comments: This enzyme, which forms part of the anaerobic (early cobalt insertion) cobalamin biosynthesis pathway, is an ATP-independent type II chelatase. Two distinct forms are known - a primordial form named CbiX, which is most common in archaea, and a strictly bacterial form named CbiK. See EC 6.6.1.2, cobaltochelatase, for the cobaltochelatase that participates in the aerobic cobalamin biosynthesis pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1. Raux, E., Thermes, C., Heathcote, P., Rambach, A. and Warren, M.J. A role for Salmonella typhimurium cbiK in cobalamin (vitamin B12) and siroheme biosynthesis. J. Bacteriol. 179 (1997) 3202-3212. [PMID: 9150215]
2. Schubert, H.L., Raux, E., Wilson, K.S. and Warren, M.J. Common chelatase design in the branched tetrapyrrole pathways of heme and anaerobic cobalamin synthesis. Biochemistry 38 (1999) 10660-10669. [PMID: 10451360]
3. Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390-412. [PMID: 12195810]
4. Brindley, A.A., Raux, E., Leech, H.K., Schubert, H.L. and Warren, M.J. A story of chelatase evolution: Identification and characterisation of a small 13-15 kDa 'ancestral' cobaltochelatase (CbiXS) in the Archaea. J. Biol. Chem. 278 (2003) 22388-22395. [PMID: 12686546]
5. Frank, S., Brindley, A.A., Deery, E., Heathcote, P., Lawrence, A.D., Leech, H.K., Pickersgill, R.W. and Warren, M.J. Anaerobic synthesis of vitamin B12: characterization of the early steps in the pathway. Biochem Soc Trans. 33 (2005) 811-814. [PMID: 16042604]
6. Lobo, S.A., Brindley, A.A., Romao, C.V., Leech, H.K., Warren, M.J. and Saraiva, L.M. Two distinct roles for two functional cobaltochelatases (CbiK) in Desulfovibrio vulgaris hildenborough. Biochemistry 47 (2008) 5851-5857. [PMID: 18457416]
7. Lobo, S.A., Videira, M.A., Pacheco, I., Wass, M.N., Warren, M.J., Teixeira, M., Matias, P.M., Romao, C.V. and Saraiva, L.M. Desulfovibrio vulgaris CbiK(P) cobaltochelatase: evolution of a haem binding protein orchestrated by the incorporation of two histidine residues. Environ. Microbiol. 19 (2017) 106-118. [PMID: 27486032]
Accepted name: GDP-mannose 3,5-epimerase
Reaction: (1) GDP-α-D-mannose = GDP-β-L-galactose
(2) GDP-α-D-mannose = GDP-β-L-gulose
Other name(s): GME (gene name); GDP-D-mannose:GDP-L-galactose epimerase; guanosine 5'-diphosphate D-mannose:guanosine 5'-diphosphate L-galactose epimerase
Systematic name: GDP-α-D-mannose 3,5-epimerase
Comments: The enzyme catalyses the formation of the stable intermediate GDP-β-L-gulose as well as GDP-β-L-galactose. The reaction proceeds by C4' oxidation of GDP-α-D-mannose followed by epimerization of the C5' position to give GDP-β-L-4-dehydro-gulose. This intermediate is either reduced to give GDP-β-L-gulose or the C3' position is epimerized to give GDP-β-L-4-dehydro-galactose, followed by C4' reduction to yield GDP-β-L-galactose. Both products serve as intermediates in two different variants of plant L-ascorbate biosynthesis pathways.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 72162-82-4
References:
1. Hebda, P.A., Behrman, E.J. and Barber, G.A. The guanosine 5'-diphosphate D-mannose: guanosine 5'-diphosphate L-galactose epimerase of Chlorella pyrenoidosa. Chemical synthesis of guanosine 5'-diphosphate L-galactose and further studies of the enzyme and the reaction it catalyzes. Arch. Biochem. Biophys. 194 (1979) 496-502. [PMID: 443816]
2. Barber, G.A. and Hebda, P.A. GDP-D-mannose: GDP-L-galactose epimerase from Chlorella pyrenoidosa. Methods Enzymol. 83 (1982) 522-525. [PMID: 7098948]
3. Wolucka, B.A., Persiau, G., Van Doorsselaere, J., Davey, M.W., Demol, H., Vandekerckhove, J., Van Montagu, M., Zabeau, M. and Boerjan, W. Partial purification and identification of GDP-mannose 3",5"-epimerase of Arabidopsis thaliana, a key enzyme of the plant vitamin C pathway. Proc. Natl. Acad. Sci. USA 98 (2001) 14843-14848. [PMID: 11752432]
4. Major, L.L., Wolucka, B.A. and Naismith, J.H. Structure and function of GDP-mannose-3',5'-epimerase: an enzyme which performs three chemical reactions at the same active site. J. Am. Chem. Soc. 127 (2005) 18309-18320. [PMID: 16366586]
5. Watanabe, K., Suzuki, K. and Kitamura, S. Characterization of a GDP-D-mannose 3'',5''-epimerase from rice. Phytochemistry 67 (2006) 338-346. [PMID: 16413588]
Accepted name: E1 NEDD8-activating enzyme
Reaction: ATP + [NEDD8 protein] + [E1 NEDD8-activating enzyme]-L-cysteine = AMP + diphosphate + [E1 NEDD8-activating enzyme]-S-[NEDD8 protein]-yl-L-cysteine
Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein
Other name(s): NEDD-activating enzyme E1; NAE1 (gene name); UBA3 (gene name)
Systematic name: [NEDD8 protein]:[E1 NEDD8-activating enzyme] ligase (AMP-forming)
Comments: Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form complexes with a cullin scaffold protein and a substrate recognition module, which are known as CRL (Cullin-RING-Ligase) complexes. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. Like ubiquitin, the NEDD8 protein ends with two glycine residues. The E1 NEDD8-activating enzyme activates NEDD8 in an ATP-dependent reaction by forming a high-energy thioester intermediate between NEDD8 and one of its cysteine residues. The activated NEDD8 is subsequently transferred to a cysteine residue of EC 2.3.2.34, E2 NEDD8-conjugating enzyme, and is eventually conjugated to a lysine residue of specific substrates in the presence of the appropriate E3 transferase (EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase).
References:
1. Osaka, F., Kawasaki, H., Aida, N., Saeki, M., Chiba, T., Kawashima, S., Tanaka, K. and Kato, S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 12 (1998) 2263-2268. [PMID: 9694792]
2. Gong, L. and Yeh, E.T. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J. Biol. Chem. 274 (1999) 12036-12042. [PMID: 10207026]
Accepted name: thioglycine synthase
Reaction: ATP + sulfide + a [methyl-coenzyme M reductase]-glycine = ADP + phosphate + a [methyl-coenzyme M reductase]-thioglycine
Glossary: thioglycine = 2-aminoethanethioic O-acid
Other name(s): ycaO (gene name) (ambiguous)
Systematic name: [methyl-coenzyme M reductase]-glycine—sulfur ligase (thioglycine-forming)
Comments: Requires Mg2+. The enzyme is found in anaerobic methanogenic and methanotrophic archaea, where it modifies a glycine residue in EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase (methyl-CoM reductase). Upon binding to its substrate, an external source of sulfide attacks the target amide bond generating a tetrahedral intermediate. The amide oxyanion attacks the γ-phosphate of ATP, releasing ADP and forming a phosphorylated thiolate intermediate that collapses to form thioglycine and phosphate. In most organisms activity requires a second protein (TfuA) , which may allosterically activate this enzyme or assist in the delivery of sulfide to the substrate.
References:
1. Nayak, D.D., Mahanta, N., Mitchell, D.A. and Metcalf, W.W. Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea. Elife 6 (2017) e29218 . [PMID: 28880150]
2. Mahanta, N., Liu, A., Dong, S., Nair, S.K. and Mitchell, D.A. Enzymatic reconstitution of ribosomal peptide backbone thioamidation. Proc. Natl. Acad. Sci. USA 115 (2018) 3030-3035. [PMID: 29507203]
3. Dong, S.H., Liu, A., Mahanta, N., Mitchell, D.A. and Nair, S.K. Mechanistic basis for ribosomal peptide backbone modifications. ACS Cent. Sci. 5 (2019) 842-851. [PMID: 31139720]
Accepted name: cyclic 2,3-diphosphoglycerate synthase
Reaction: ATP + 2,3-diphospho-D-glycerate = ADP + phosphate + cyclic 2,3-bisphosphoglycerate
Other name(s): cpgS (gene name)
Systematic name: (2R)-2,3-bisphosphoglycerate ligase (cyclizing)
Comments: The enzyme is present in a number of methanogenic archaeal genera that accumulate cyclic 2,3-bisphosphoglycerate as a thermoprotectant. Activity is stimulated by potassium ions.
References:
1. Lehmacher, A., Vogt, A.B. and Hensel, R. Biosynthesis of cyclic 2,3-diphosphoglycerate. Isolation and characterization of 2-phosphoglycerate kinase and cyclic 2,3-diphosphoglycerate synthetase from Methanothermus fervidus. FEBS Lett. 272 (1990) 94-98. [PMID: 2226838]
2. Matussek, K., Moritz, P., Brunner, N., Eckerskorn, C. and Hensel, R. Cloning, sequencing, and expression of the gene encoding cyclic 2,3-diphosphoglycerate synthetase, the key enzyme of cyclic 2,3-diphosphoglycerate metabolism in Methanothermus fervidus. J. Bacteriol. 180 (1998) 5997-6004. [PMID: 9811660]